INHIBITORY EFFECT OF ZINC ON STIMULATED ERYTHROPOIETIN SYNTHESIS IN HEPG2 CELLS

The effect of zinc on erythropoietin (EPO) synthesis in HepG2 cells was investigated. The increase in EPO synthesis induced by Co2+ (50-mu-m), Ni2+ (300-mu-M) or oxygen (1% O2) was inhibited by the presence of ZnCl2 (50-150-mu-M) in the tissue-culture medium, whereas basal EPO synthesis was unaffected. The effect was reflected by corresponding changes in the EPO mRNA level. These effects of zinc on EPO synthesis could not be mimicked by CdCl2 (less-than-or-equal-to 2-mu-M). Addition of FeCl3 to the medium appeared to decrease the inhibitory effect of zinc on hypoxia-induced EPO synthesis, implying that zinc may interfere with an iron-dependent step in EPO regulation.